The proposed research is designed to study the regulation of the citric acid cycle of Bacillus subtilis. The isolation and characterization of regulatory mutants is planned. These mutants will be isolated by selection for resistance to specific analogues and inhibitors and by reversion of leaky mutants. A program is outlined to study the control of enzyme synthesis in the citric acid cycle by means of derepression studies. These studies will utilize single and double mutant blocks of selected enzymes in the cycle to allow control of the levels of intracellular intermediates. By means of derepression studies and regulatory mutants the intermediates responsible for repression will be established. Regulation of the enzymatic activity of key enzymes by intermediates and nucleotides will be determined and a search for enzyme complexes will be undertaken. The role of the citric acid cycle in the developmental sequence of sporulation will be ascertained.